Even though tumors originate from normal cells, the immune system often reacts relatively strongly against tumor cellular components. However, because the tumors closely resemble the original cells, the immune system tolerates many tumor types to a variable degree. Thus, the very nature of tumor immunity poses enormous challenges to harnessing the immune system for the therapy of cancers. Recent studies have indicated that immunologic targeting of cancer is a promising strategy (Hodi, F. S., et al. N Engl J Med 363, 711-723 (2010)); however, how best to achieve this goal is incompletely understood.
The use of mouse melanoma models is a convenient way to study tumor immunity. Melanoma is a malignant tumor of melanocytes. Primarily melanoma is a skin tumor, but it is also seen, though less frequently, in the melanocytes of the eye (uveal melanoma). Even though melanoma represents one of the rarer forms of skin cancer, it underlies the majority of skin cancer-related deaths. Yet despite many years of intensive laboratory and clinical research, there are still limited treatments for melanoma, and the treatments exhibit resistance and multiple unwanted side effects including back pain, constipation, cough, diarrhea, dizziness, dry skin, hair loss, headaches, joint or muscle pain, loss of appetite; nausea, taste changes, thickening of the skin, tiredness, vomiting, weakness, and severe allergic reaction (e.g. Zelboraf™ (Vemurafenb or PLX4032: Hoffman-La-Roche (Madison Wis.)/Daiichi Sankyo (Parsippany, N.J.)).
Thus, there is a need for a better understanding of tumor immunity in order to facilitate efficient harnessing of this aspect of immune system as an effective therapy for the treatment of cancer.